A 42-year-old man presents with a 3-year history of progressive bilateral hearing loss and recurrent episodes of vertigo with imbalance in the dark. Audiometry shows bilateral high-frequency sensorineural hearing loss with downsloping pattern. Caloric irrigation reveals bilateral reduced responses. His father had similar symptoms starting in his 40s. The clinical presentation marked as **A** in the diagram — progressive high-frequency SNHL with bilateral vestibulopathy — is most consistent with which genetic disorder?

Why DFNA9 (COCH gene mutation on chromosome 14q12) is right

DFNA9 is the most common autosomal dominant cause of late-onset progressive sensorineural hearing loss with vestibular dysfunction, presenting in the 4th–6th decades. The COCH gene (chromosome 14q12) encodes cochlin, the most abundant protein of the inner ear extracellular matrix. Pathogenic missense mutations cause misfolding and dominant-negative deposition of mutant cochlin as eosinophilic aggregates in the spiral ligament and vestibular labyrinth. The clinical hallmark is insidious onset with bilateral progressive high-frequency downsloping SNHL combined with bilateral peripheral vestibulopathy (instability in the dark, oscillopsia, recurrent vertigo), exactly matching the presentation marked A. The positive family history (father affected in 4th decade) confirms autosomal dominant inheritance. This patient requires genetic testing (COCH sequencing), annual audiometry and vestibular reassessment, hearing aids or cochlear implantation as needed, vestibular rehabilitation, and genetic counseling for his children (50% recurrence risk).

Why each distractor is wrong

Cummings Otolaryngology 7e; Smith RJH GeneReviews — DFNA9 COCH 2024